The past year saw manufacturing challenges pushed into the spotlight. BioSpace spoke to two executives who shared key issues facing those working in this area, from finding the right providers to dealing with regulatory uncertainty.
While manufacturing professionals face multiple challenges as they help bring products to patients, three stand out, based on BioSpace interviews with two biopharma executives. Two involve working with manufacturing providers while the third is tied to regulatory issues.
To explore these challenges, BioSpace spoke to Rich Kenley, vice president of chemistry, manufacturing and controls at Actuate Therapeutics, and Ryan Pruchnic, managing vice president of Cook MyoSite. Fort Worth, Texas–based Actuate is a biotech that develops therapies for the treatment of high-impact, difficult-to-treat cancers. Cook MyoSite is a Pittsburgh-based company that develops and commercializes technology related to the collection, selection and expansion of human skeletal muscle cells for regenerative medicine applications.
Finding Sterile Product Manufacturers
Finding providers to make sterile products has become exceedingly difficult, according to Kenley.
“In the sterile manufacturing world, the issue is that the introduction of the GLP-1 sterile products has created such a demand for capacity that it’s squeezing out available capacity for smaller products,” he told BioSpace.
Kenley noted that companies like Eli Lilly and Novo Nordisk consume a huge amount of sterile manufacturing capacity. Lilly’s GLP-1 portfolio includes blockbuster drugs Zepbound and Mounjaro, while Novo’s has blockbuster drugs Ozempic and Wegovy.
Novo’s impact on sterile product manufacturing capacity has shown up in another way as well, Kenley noted. In 2024, Novo Holdings bought Catalent, a contract development and manufacturing organization (CDMO), and then sold three of the CDMO’s fill-finish sites to Novo Nordisk. That deal, Kenley said, wiped out a huge service provider to biopharmas.
For startups and development-stage companies looking for providers to manufacture sterile products, Kenley offered some advice. Given that those businesses won’t make huge amounts of product or huge numbers of batches for the next several years, he said, they should connect with niche—rather than big, high-capacity—providers.
“They may be limited in scale eventually, but they’re still available to take on startup projects,” Kenley said.
Deciding Where To Manufacture Small Molecule APIs
When it comes to manufacturing small molecule active pharmaceutical ingredients (APIs), Kenley noted that by far, the greatest capability and capacity is in China. In addition, he said, it costs less to produce organic chemistry molecules in that country than in the U.S. and Europe. A major challenge with using providers in China, however, is the BIOSECURE Act.
Created to restrict biopharma companies from working with Chinese firms and enacted into law in December, the act does not name which businesses are considered a “biotechnology company of concern.” Such firms are identified on an annual list published in the Federal Register by the Department of Defense. The Office of Management and Budget can add or remove companies from that list after consulting with other federal agencies.
“So, pharmaceutical developers don’t know what the future holds,” Kenley said. “Is a company I’m using today in China to make my API going to be on their list next year? And what do I do about that? There’s solutions always to this problem, but onshoring it takes time and costs money that development-stage companies usually don’t have.”
Kenley advised that companies just starting to develop small molecule products avoid manufacturing in China and consider India instead, as that country has a large API manufacturing capacity. If businesses are already in production in China, he said the situation is more difficult because investors will want to know what they’ll do if the Chinese partner is named a biotechnology company of concern. For those companies, Kenley recommended developing fallback positions to protect against investor fallout, such as contacting firms in India that make the same product or looking into moving production to the U.S.
“Of course, that’s not as simple as it sounds, because China still makes most of the world’s starting materials—the raw materials that go into making the drug—and a lot of that is proprietary,” Kenley said. “So, it’s not necessarily obvious all the time how you would onshore the manufacturers.”
Dealing With Regulatory Issues
Regulatory issues are also a hurdle for manufacturing professionals, according to Kenley and Pruchnic. Kenley noted that there’s always a challenge in trying to figure out how U.S. and especially European authorities are going to respond. Oftentimes, he said, there are slight but nagging and annoying differences between the two. In addition, Kenley noted, the Trump administration and subsequent FDA shakeups have added a level of uncertainty the industry didn’t have before.
“The system wasn’t perfect, but at least you more or less knew what it was,” he said. “The rules are really in flux right now.”
The uncertainty stems from issues including regulatory guidance reversals. For example, in October, uniQure announced the FDA had changed its tune on the evidence it required for the company’s biologics application submission for a Huntington’s disease gene therapy.
Uncertainty is also linked to reorganizations at the FDA, which by early July had resulted in about 3,500 employees out of work. Kenley noted that because of those changes, some biopharmas, including Actuate, wound up working with different people at the agency than they’d started with, resulting in the need to forge new relationships.
Regarding rules that are in flux, the FDA on Jan. 11 announced it will relax some of its chemistry, manufacturing and control requirements for cell and gene therapies. For example, when investigational gene therapies advance past Phase I, the agency won’t require manufacturers to comply with certain manufacturing specifications for biologics as outlined in Chapter 600 of the Coe of Federal Regulations.
In emailed responses to BioSpace, Pruchnic cited challenges with the regulations themselves for companies like Cook MyoSite. He noted that even though regulations have begun to catch up with manufacturing regenerative medicine products, there’s still a lot of ambiguity in what’s expected versus what’s reality.
“For instance,” Pruchnic wrote, “clear and understandable regulations exist stating you cannot have particles in pharmaceutical products. These same expectations exist in cell therapies, when in fact a cell is a particle in the product. You must then interpret where ‘a certain limit is acceptable’ but there are not always clear directives to follow.”
Because there’s not always clarity, Pruchnic said, companies must try to cover regulations as well as they can, which can lead to countless experiments, quality system builds and rebuilds and regulatory documentation uncertainty. That’s a challenge for products that are expensive and arduous to manufacture, he noted.
To best deal with regulatory issues, Kenley recommended companies hire expert consultants that can help them navigate the strategic waters through the FDA with all the changes going on at the agency. Many of these consultants talk to regulators and are therefore close to the issues, he noted.
Pruchnic also offered advice, emphasizing the value of companies advocating for themselves with the FDA.
“You are the expert of your product,” he wrote. “Build processes that you believe in and can defend with science. Then go make a strong argument for why you are right. If you wait to have someone else tell you what is right or wrong, you may be depending on someone that has far less experience on your product than you do.”
